The chemical compound 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0]octan-3-one (also known as ethoxyheptyl bicyclooctanone or ETHOCYN®) is a non-steroidal compound that penetrates into the dermis. CYOCTOL™ or 6-(5-methoxyhept-1-yl)bicyclo[3.3.0]octan-3-one is a similar compound. These compounds competitively inhibit intercellular dihydrotestosterone (DHT) receptor binding in fibroblasts derived from cutaneous tissues and has been investigated for treatment of DHT-mediated medical disorders, such as acne vulgaris, hirsuitism, androgenetic alopecia, and keloid scars.
The synthesis of 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0]octan-3-one is complex due to, e.g., the compound's bicyclic structure, which includes four chiral centers. The synthesis includes multiple reactions, some of which are expensive or dangerous. One of the reactions includes a ring expansion reaction using etheral diazomethane, which is produced from DIAZALD® (N-methyl-N-nitroso-p-toluenesulfonamide) and ethanolic potassium hydroxide. The diazomethane reaction is highly toxic and dangerous, due to the explosive potential of the reaction. Methods of synthesizing 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0]octan-3-one and derivatives are described in U.S. Pat. No. 4,689,349 to Kasha et al. Methods of synthesizing a derivative of 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0]octan-3-one, (6-(5-methoxyhept-1-yl)bicyclo[3.3.0]octan-3-one or CYOCTOL™), are also putatively described in Mulzer et al., “Stereocontrolled synthesis of all eight stereoisomers of the putative anti-androgen cyoctol,” Tetrahedron 60:9599-9614 (2004).